SYNTHESIS: A well-stirred solution of 0.45 g free base DOB in 2 mL
CH2Cl2 was treated with 0.37 g triethylamine, cooled to 0 °C, and
there was then added a solution of 0.39 g
1,1,4,4-tetramethyl-1,4-dichlorodisilylethylene in 2 mL CH2Cl2. The
reaction mixture was allowed to return to room temperature, with
stirring continued for 2 h. The solvent was removed under vacuum, the
residue suspended in hexane, and the insoluble by-products removed by
filtration through celite. Removal of the solvent under vacuum gave
0.60 g
1-(4-bromo-2,5-dimethoxyphenyl)-2-(1-aza-2,5-disila-2,2,5,5-tetramethylcyclopentyl)propane
as a gold-colored impure semi-solid mass which was used without
further purification.
To a solution of 0.60 g
1-(4-bromo-2,5-dimethoxyphenyl)-2-(1-aza-2,5-disila-2,2,5,5-tetramethylcyclopentyl)propane
in 10 mL anhydrous Et2O under an inert atmosphere and cooled to -78 °C
there was added 1.8 mL of a 1.7 M solution of t-butyl lithium in
hexane. The resulting yellow solution was stirred for 20 min, and
then treated with 1.65 mL of a 1.4 M solution of ethylene oxide in
Et2O, the stirring was continued for 40 min, then the reaction mixture
allowed to come to room temperature over an additional 40 min. There
was added 20 mL hexane, and the temperature increased to 50 °C for an
additional 2 h. The reaction mixture was treated with 3 mL H2O and
diluted with 60 mL Et2O. The organic phase was washed with saturated
NH4Cl, dried over anhydrous MgSO4, and after filtering off the
inorganic drying agent, the organic solvents were removed under
vacuum. The gold-colored residual oil was dissolved in 10 mL MeOH and
treated with a 10% KOH. This mixture was heated for 30 min on the
steam bath, returned to room temperature, and the volatiles removed
under vacuum. The residue was dissolved in 3% H2SO4, washed twice
with CH2Cl2, brought to pH 12 with 25% NaOH, and extracted with 3x50
mL CH2Cl2. The pooled extracts were combined, dried with anhydrous
Na2SO4, and the solvent removed under vacuum to give 0.24 g of
2,5-dimethoxy-4-(2-hydroxyethyl)amphetamine (DOEH) as a white solid
with a mp of 102-104 °C.
To a suspension of 0.94 g DOEH in ice-cold anhydrous Et2O containing
1.4 g triethylamine, there was added 2.4 g trifluoroacetic anhydride
dropwise over the course of 10 min. The reaction mixture was brought
to reflux temperature, and held there with stirring for 1 h. After
cooling, 60 mL of CH2Cl2 was added, and the organic phase washed with
saturated NaHCO3. The solvent was removed under vacuum, providing a
gold-colored solid as a residue. This was dissolved in 50 mL MeOH,
diluted with 30 mL H2O and, following the addition of 0.76 g solid
NaHCO3 the reaction mixture was stirred at room temperature for 3 h.
The excess MeOH was removed under vacuum, and the remaining solids
were suspended in CH2Cl2 and washed with H2O. After drying the
organic phase with anhydrous Na2SO4 and removal of the solvent under
vacuum, there was obtained 1.34 g
1-(2,5-dimethoxy-4-(2-hydroxyethyl)phenyl)-2-(2,2,2-trifluoroacetamido)propane
as white solid with a mp of 129-131 °C. Anal. (C15H20F3NO4) C,H.
A well-stirred solution of 0.09 g
1-(2,5-dimethoxy-4-(2-hydroxyethyl)phenyl)-2-(2,2,2-trifluoroacetamido)propane
in 15 mL CH2Cl2 was cooled to -78 °C and treated with 0.05 g
diethylaminosulfur trifluoride (DAST) added dropwise. The pale yellow
reaction solution was stirred an additional 5 min and then brought up
to room temperature and stirred for 1 h. There was then added
(cautiously) 3 mL H2O followed by additional CH2Cl2. The phases were
separated, the organic phase washed with H2O, dried with anhydrous
Na2SO4 and, after filtering off the drying agent, stripped of solvent
under vacuum. There was thus obtained 0.088 g of
1-[2,5-dimethoxy-4-(2-fluoroethyl)phenyl]-2-(2,2,2-trifluoroacetamido)propane
as a white solid with a mp of 102-104 °C.
A solution of 0.12 g
1-[2,5-dimethoxy-4-(2-hydroxyethyl)phenyl]-2-(2,2,2-trifluoroacetamido)propane
in a mixture of 5 mL CH2Cl2 and 5 mL IPA was treated with 0.2 mL 2 N
KOH, heated on the steam bath for 30 min, and then stripped of
solvents under vacuum. The residue was suspended in CH2Cl2 and washed
with 20% NaOH. The organic phase was dried with anhydrous Na2SO4
which was removed by filtration, and the combined filtrate and
washings stripped of solvent under vacuum. The residual glass (0.08
g) was dissolved in IPA, neutralized with concentrated HCl and diluted
with anhydrous Et2O to provide
2,5-dimethoxy-4-(2-fluoroethyl)amphetamine hydrochloride (DOEF) as a
white crystalline solid with a mp of 205-208 °C. Anal. (C13H21ClFNO2)
C,H.
DOSAGE: 2 - 3.5 mg.
DURATION: 12 - 16 h.
QUALITATIVE COMMENTS: (with 2.2 mg) Somewhere between the first and
second hour, I grew into a world that was slightly unworldly. Why?
That is hard to say, as there was no appreciable visual component. I
just knew that the place I was in was not completely familiar, and it
was not necessarily friendly. But it was fascinating, and the music
around me was magical. Time was moving slowly. I had to drive across
the bay at about ten hours into this, and I was comfortable. That
evening I slept well, but my dreams were pointless.
(with 3.0 mg) It took almost three hours to full activity. The first
signs of effects were felt within a half hour, but from then on the
progress was slow and easy, without any discernible jumps. There was
absolutely no body discomfort at all. Completely comfortable. There
was a general humorousness about my state of mind which is always a
good sign. We went to the bedroom at the two and a half hour point,
and proceeded to establish that the material is far from anti-erotic.
Beautiful response, without a mention of any feeling of risk at
orgasm. I myself was not able to reach orgasm until about 5th to 6th
hour, and then it was full and exceptionally delicious. So was the
second one, a couple of hours later, if I remember correctly. All
systems intact, body, mind and emotion. Gentle. Good for writing.
No dark corners apparent at all. For me, not highly visual. Would
take again, higher.
(with 3.0 mg) There was no body threat at any time--very
comfortable. Good eyes closed, with complex imagery to music, but not
too much with eyes-open. My attention span is relatively short, and
easily diverted into new directions--all quite reminiscent of DOI
both as to dosage and effect. At 13 hours, I am still too alert to
sleep, but a couple of hours later, OK. In the morning there is still
a trace of something going on. This was a valid +++.
EXTENSIONS AND COMMENTARY: I was asked by a student of mine a while
ago, when I told him of this material, just why would anyone just
happen to place a fluorine atom at the end of the 4-ethyl group of
DOET? It wasn't the sort of thing that someone would just happen to
do. If there were a rationale, then that's fine. But by capricious
impulse, no. But there is a rationale of sorts, which I just hinted
at in the discussion under 2C-T-21.
This argument of reason goes as follows. Assume that I would like to
put a fluorine atom into a drug that does not normally have one. Why
would I want to? Because I want to have the molecule carry a
radioactive fluorine atom into some inner recess of the brain. Why?
Because by using a positron-emitting fluorine I could possibly
visualize the area of the brain that the drug went to. And if it went
there in some abnormal way, the exact measure of that abnormality
might give some clue as to potential brain misfunctioning.
But, if you put a fluorine atom on a drug, it becomes a totally new
drug and, quite reasonably, a pharmacologically different drug.
However, a body of evidence is being accumulated that if a halogen,
such as a bromine or an iodine atom, is replaced by a beta-fluoroethyl
group, the electronic and polar properties of the drug can be pretty
much the same. So, what psychedelics have a bromo or an iodo group?
Obviously, DOB and DOI. Thus, DOEF is a natural candidate for
fluorine-18 positron emission tomography, and also a natural candidate
for clinical trials. And, voila, it is an active material.
And I'll bet you dollars to doughnuts, that if one were to make the
two-carbon analog 2,5-dimethoxy-4-(2-fluoroethyl)-phenethylamine, it
would be every bit as much a treasure and ally as is 2C-B or 2C-I. In
fact, I am sure enough about this prediction that I am willing to name
the stuff 2C-EF. It will be easily made from 2C-B by the same
reaction scheme that was used above for DOEF. And I will even guess
that its activity level will be in the 20-30 milligram area.
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